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by zug_zug·2mo ago·view on hn ↗
>> Recently, a pilot study (single-arm) by Smith et al., recruited 20 patients (73 years of age) with AD and provided them with 20 grams/day of CrM for 8 weeks [20]. Serum creatine levels were increased at weeks 4 and 8 (p < 0.001), and total brain creatine levels (as measured by H-MRS) increased by 11% (p < 0.001). Clinically, there were demonstrated improvements in cognition on global (p = 0.02) and fluid composites (p = 0.004), as well as List Sorting (p = 0.001), Oral Reading (p < 0.001) and Flanker tests (p = 0.05).

Yeah 20 patients is not a lot. I'm inferring this is a pre-post test. However some of those p-values are pretty good (.001 on reading and and sorting). Very promising pilot study but not conclusive imo.

3 comments
19 patients completed, according to the article.

And List Sorting, Oral reading, and Flanker only? The first and last are part of global and fluid composites, so those have to be excluded from comparison. That leaves us with 3 improved scores out of 12 tests. So 9 did not improve, or got worse. Figure 3 (of the original article) shows that the changes aren't big. Just "significant". Since the participants were in the early stages of dementia, this seems well within expectations.

So I can't see those numbers as impressive.

I can’t help but feel that the participants being in the early stage of dementia is a lede being buried. Perhaps I’m misunderstanding.
Sounds like something we should study more rather than dismiss.
This study holds little promise at first sight. Remember that there is a lot to study, and only limited research capability.

> Sounds like something we should study more rather than dismiss.

Ignoring the implication of your use of "dismiss", why? How is this pilot promising?

Sounds like something that should fly under a different headline until then.
Interesting that you are hearing "dismissal" in the antecedent response. I read it as the poster "studying more" the data, and finding a lot of flaws in both the experimental design and the data analysis.Typically things a reviewer would do when a publication was submitted (or in our case posted here). The author, then goes back and answers the questions raised to show that the effect they are suggesting is durable in face of the flaws. Or perhaps they run an additional experiment and augment their data. After a bunch of back and forths either the effect is sufficiently well expressed in the data or the paper is withdrawn for more work.

When I go through the process of reading the entire paper, analyzing the data myself, and the experimental design. That is the opposite of dismissing the claim. That is me, positing that the claim as stated is 'true,' and then asking the questions if the claim is supported by the provided evidence. If it isn't, then doing the work to express what evidence would be needed to support the claim is the feedback needed to help prove the science.

Don't waste your time responding to people like this. Their post is not much more than a passing thought where they take the headline fully at face value, and therefore are convinced it must be worth something and we should continue to study it. They will never read the paper or have a critical thought of their own.
I don’t really leave thank you notes as they don’t add anything but just to balance out the opinions here:

Thank you for taking the time for that wonderful explanation, may it teach some of us/me to think before we shoot. I found it very enlightening and am sure many other drive by casuals do as well.

Creatine effects vary a lot from person to person. It isn't all that harmful and easy to notice. Best test it yourself.

I apparently produce much less than I can use. Effect is in the, how is this even legal? range.

I wouldn't even call it "promising but inconclusive" so much as "not conclusively a dead-end for further research". In a single-arm open-label study, with no blinding, both the participants and the researchers know who's getting what. You need a placebo and double-blinding for comparison against the active group and to adjust for any ways in which the researchers may have unwittingly influenced the results. (Or perhaps even wittingly, when there are conflicts of interest. I spent half a minute looking up this study and didn't see any statement attesting that there were none.)
Worse: go look at the MMSE. I bet that, at least for patients with reasonably functional memory, taking the MMSE and then taking it again a few weeks later from the same examiner will tend to improve the score the second time.
One study rarely makes or breaks anything. Creatine has lots of studies going back 10-20 years.
.001 for creatine levels isn't surprising; that's a lot of creatine. I'd explain the cognitive tests with the practice effect, because it is unlikely that creatine had such a massive effect and we only discover it now.
I hear about tech bros taking creatine these days with the tone of voice that they use to talk about microdosing. So I can’t imagine it having zero effect.

What I worry about more is that it has more to do with fixing a deficiency. That being deficient in creatine causes a cognitive loss more than supplementing causes a boost.

As someone who's microdosed (though mostly normal-dosed and occasionally megadosed) in the distant past, the whole microdosing fad was equal parts entertaining and baffling. Anecdotal, but from all people I know that has taken psychedelics, only one doesn't find it to be a waste.
Maybe a better analogy would have been the Balmer curve. I wasn’t trying to imply psychedelics are unhelpful, just that we should be careful of suggesting coding productivity gains while on them.

Also IMO, the Balmer peak is a stronger effect than creatine.